The proposal seeks funding for an MR-guided Focused UltraSound (MRg-FUS) system (ExAblate(R) 2000, Insightec Inc.) for use with a newly installed state-of-the-art 3T MRI scanner at the University of California San Francisco Medical Center. The long term objective is to develop a multidisciplinary MRg-FUS program at UCSF which will conduct clinical research into a broad spectrum of oncological applications, with the goal of improving the care of patients with cancer by translating this novel therapeutic technology for tumor ablation from basic investigational studies to daily clinical practice. In the near term, we plan two major specific clinical applications: Provision of a novel minimally invasive "middle way" of focal therapy for low risk prostate cancer that bridges the current gap between conservative active surveillance and aggressive high morbidity definitive therapy by surgery or radiation. The MRg-FUS system will be specifically equipped to perform endorectal ablation of prostate cancer. We plan a clinical study investigating the role of focal therapy for tumor ablation in patients with radiologically visible and clinically low risk tumors. Implement a pain palliation service for patients with symptomatic bony metastases that are refractory to standard therapy. As part of the development of this service, we will participate in a multicenter study to evaluate the effectiveness and safety of MRg-FUS treatment of metastatic bone tumors for the palliation of pain in patients who are not candidates for radiation therapy. The study hypothesis is that treatment with MRg-FUS is a safe and effective noninvasive treatment for painful bone metastases. High energy focused ultrasound is a completely incisionless and non-invasive method for percutaneous or endoluminal targeted tissue ablation, with no ill effects on adjacent tissue. This technology avoids the tissue toxicity and morbidity associated with traditional methods of tumor ablation by surgery, radiation, embolization, radiofrequency ablation, or cryoablation. MR guidance provides two additional major advantages - accurate tumor visualization and targeting and real time MR thermometry for precisely controlled and monitored thermal therapy. The researchers brought together in this grant are a large, well-funded, established, multidisciplinary group with extensive related publications and research interests. If MRg-FUS is to fulfill its promise as the non- invasive and incisionless surgery of the future, then these investigators and UCSF are the natural team and place to scientifically test and develop this technology. The system will also provide direct and immediate translational impact, allowing for the provision of new and exciting therapeutic options for patients with cancer. These advances are completely aligned with the long range goals of the NIH, in that they emphasize interdisciplinary and translational research that offers immediate patient benefit and provides a novel minimally invasive therapeutic approach to diseases of major socioeconomic importance. PUBLIC HEALTH RELEVANCE: The instrument requested in this grant is an MR-guided Focused UltraSound (MRg-FUS) system, a new technology which allows certain sites of cancer in the body to be killed by high energy sound waves transmitted through a probe placed on the skin or in the rectum, offering the hope of completely incisionless surgery in selected patients (we will initially treat patients with low risk prostate cancer and painful bone cancers). The MRI scanner allows the tumor to be accurately targeted and killed, with minimal risk of damaging anything other than the tumor. This grant will generate or sustain over 25 jobs, and uses a technology that creates little or no biohazardous waste and does not use ionizing radiation.